Significant changes in the cyclic AMP-dependent phosphorylation of specific plasma membrane proteins associated with malignant transformation have recently been identified in my laboratory and we have shown that aberrant activity of an endogenous plasma membrane cyclic AMP-dependent protein kinase is responsible for these changes. We have also identified differences in the cyclic AMP-dependent phosphorylation of plasma membrane proteins in differentiated and undifferentiated cells and have shown that modulation of cyclic AMP-dependent plasma membrane protein phosphorylation occurs during the G1 phase of the cell cycle in non-transformed cells. Studies proposed in this grant are designed to test the hypothesis that specific plasma membrane phosphoproteins influence control of cell growth in nontransformed cells but not in transformed cells. Experiments will be performed to characterize the endogenous cyclic AMP-dependent phosphorylation system in a variety of cell systems and to identify the biochemical basis for the defect in the phosphorylation system in transformed cells; both the protein kinase and its plasma membrane substrate will be studied. We will also examine the mechanisms for regulation of this phosphorylation system and we will attempt to identify the function(s) of the plasma membrane phosphoproteins especially their role in control of DNA synthesis and cell cycle kinetics.